science/technology the potential to push through thousands of potential candidates that can be screened in a short amount of time. "The major thing is, how large a piece of landscape can we search through with limited time?" says Xiang. "This whole trend is basically a promise that we can increase the material discovery rate by a factor of 1,000 to 100,000." Materials that have specific magnetic, conducting, or optical properties lend themselves especially well to mass screening methods, because the probes for those properties are simple, says DiElizabeth K. Wilson California, Berkeley, chemistry professor Salvo. Potential phosphors—used for C&EN West Coast News Bureau Peter G. Schultz, a leading developer of many display technology applicationscombinatorial chemistry technology and a are a case in point. They can be screened by simply seeing which lights up the ombinatorial chemistry, the fairly cofounder of Symyx. recent technology that rapidly In the case of drug development, brightest in response to photoexcitation. The typical combinatorial approach and automatically makes and chemists are concerned primarily with screens thousands of compounds for compounds that selectively bind to specif- to materials science is to create a "lispecific properties, has been applied al- ic targets. Materials scientists, Schultz ob- brary" of related materials by depositing most exclusively as a method for drug serves, are searching for substances with varying ratios of substances in arrays on discovery. But perhaps an even richer numerous electronic, magnetic, and opti- a substrate. The materials then are propotential for discovery lies in the broad cal properties, and for heterogeneous cat- cessed thermally to mix them and form area of materials science. Researchers alysts and alloys. "There's a huge number compounds. The combinations are produced through a series of masks that are showing that combinatorial chemis- of things to look at," he says. try could be a powerful method for In this field, however, as Francis J. yield thousands of permutations. "Through mining that potential. DiSalvo Jr., chemistry professor at Cor- a small number of steps, you end up The scientific and technological nell University, puts it, "trying to find with a much larger number of different world is always on the lookout for bet- new structures and scan for new phe- combinations," Xiang says. ter, more efficient electronic and mag- nomena is a slow process." The library is then screened for the netic devices, phosphors, superconducResearchers doggedly pursue one ma- desired properties, and the winning cantors, and catalysts. And the nascent com- terial at a time, without any prior assur- didates are studied more thoroughly. The binatorial efforts by a few groups are ance that it will actually work. If it technology has some sticking points; for producing results. doesn't, they're back to the drawing example, there's the question of whethLast May, physicist Xiao-Dong Xiang board. But combinatorial chemistry has er small blobs of material that show and colleagues at Lawrence promise could be syntheBerkeley National Laboratory sized easily—or behave in (LBNL) in California anthe same manner—in bulk. nounced discovery of effiThe entire field of combicient green, blue, and red natorial chemistry is young. In phosphors by using combi1988, biochemist and biotechnatorial methods [Appl. nology entrepreneur AlejanPhys. Lett., 70, 3353 (1997)]. dro C. Zaflaroni founded AffyRight on their heels, Santa max N.V., Amsterdam, and its Clara, Calif.-based Symyx subsidiary Anymax Research Technologies—a company Institute, Palo Alto, Calif., for devoted solely to using comthe purpose of combinatorial binatorial methods for matedrug discovery. rials discovery—also uncovThen, less than three ered a red phosphor [Nayears ago, Schultz, Xiang, ture, 389, 944 (1997)]. And and colleagues first reported many more such papers are their combinatorial approach waiting in the wings for pubto materials discovery [Scllication, scientists in the field era*?, 268, 1738 (1995)]. say. Soon after, Schultz and Zaffaroni founded Symyx "I think the application of with the goal of developing combinatorial methods to and applying combinatorial materials is potentially more chemistry techniques and scientifically exciting than A combinatorial library of potential phosphors created by Symyx high-throughput analysis for the application to drug dis- Technologies fluoresces under UV excitation. The brightest materials discovery. LBNL covery," says University of fluorescence Indicates the most promising candidates.
COMBINATORIAL CHEMISTRY
Notjust for drug discovery, high-throughput technique gains favor in materials research for electronic, magnetic, and optical devices
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24 DECEMBER 8, 1997 C&EN
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sibility for alkanes to be dehydrogenated efficiently without use of a hydrogen ac ceptor," he explains. The complex was first generated by A catalytic system based on iridium effi Kaska in Santa Barbara. Later, Jensen's ciently converts alkanes to alkenes with group, in collaboration with Kaska, iso out requiring a hydrogen acceptor, a re lated and purified the catalyst, estab cent study shows. The catalyst could lished its high-temperature stability, and prove useful in industrial production of showed that it can efficiently catalyze versatile alkene feedstocks from alkanes transfer dehydrogenation of cyclooctane. as well as in practical hydrogen storage Now, in a wider collaboration with Gold man, the researchers demonstrate the systems. Removing hydrogen from alkanes to catalyst's ability to carry out acceptorless produce alkenes requires a lot of energy dehydrogenations of cycloalkanes (Cbem. and occurs only at temperatures exceed Commun., 1997, 2273). The reactions are very endothermic, ing 400 °C in the presence of metal cata lysts. The energy cost may be lowered by requiring up to 30 kcal per mole, an en irradiating the reaction with ultraviolet ergy barrier that the catalyst "literally light or by using a hydrogen acceptor. In brings down to the thermodynamic min the latter method, called transfer dehy imum," says chemistry professor William drogenation, the reaction includes a sac- D. Jones II at the University of Rochester. "That's impressive," he adds. Y A1 La E VO w a S Γ ( 0.8845 0.070 0.060 U 0 .025 4) Ρ Such a stable catalyst is duced by its automated combinatorial of potential interest to in method that produces thin-film libraries dustry, says Roy A. Periana, of up to 25,000 different materials on a director of research at Cat3-inch-diameter substrate. alytica Advanced Technolo The firm is refining the automation gies, Mountain View, Calif. and screening technologies, setting up But he says more work systems that allow superhigh throughput must be done before it can and "a real production running mode," be of practical use. say Jeryl L. Hilleman, Symyx's vice presi One issue is catalytic dent and chieffinancialofficer, and Xin rates. Although "not to be D. Wu, Symyx's director of electronic sneezed at," says Periana, materials. "This is the discovery stage," Hilleman Jensen (left) and Goldman: same reaction, different reasons the rates achieved so far are two to three orders of says. Although a few industrial giants such rificial alkene that receives the hydro magnitude slower than they need to be. Another problem is efficiency. Con as DuPont and Kodak are purportedly us gens removed from the alkane. Neither method is ideal: Photochemis version drops after several hundred turn ing some aspects of combinatorial meth ods for developing very specific sub try is not widely applied in industry, and overs. But it's not because the catalyst stances, such as catalysts or high dielec use of a sacrificial acceptor is wasteful. decomposes with time, as happens with tric constant films, the general feeling in Researchers have been seeking catalysts many catalysts for alkane functionalizaindustry is one of caution, DiSalvo says. that allow acceptorless reactions at con tion, says Goldman. It appears the alkene product inhibits the catalyst by tying up They want to see whether the technolo ditions milder than currently practiced. gy will work, scientifically and financial An exceptionally robust five-coordi coordination sites. "I see it as a mild inhibitory effect," ly, on a production scale. nate iridium complex with two sites oc "A lot of people are waiting to see cupied by hydrogen and three sites by says Jones, who notes that the catalyst what happens at Symyx," DiSalvo says. the "pincers" of the ligand η 3 - slows down when the alkene concentra "If it hits a home run, then I think more C6H3[CH2P(fc^-C4H9)2]2 may be such a tion is about 5 to 10%. "That's a useful people will get into it, and it will be eas catalyst, according to research from the enough concentration" to allow removal ier to attract funding." labs of chemistry professors Craig M. of the product by distillation or some As more discovery papers are pub Jensen at the University of Hawaii, other means, he says. In addition, the catalytic system needs lished, the ice may soon break, DiSalvo Manoa, in Honolulu, and William C. Kasand Schultz say. "People are paying at ka at the University of California, Santa to be tested with linear alkanes. "That's tention—some who pooh-poohed it two Barbara, and associate chemistry profes where the action is from an industrial years ago are saying now that maybe sor Alan S. Goldman at Rutgers Universi point of view," says Periana. there's something there," DiSalvo notes. ty, New Brunswick, N.J. Although interested in the same reac And what will really make the field The catalyst is stable even at 200 °C— tion, Goldman and Jensen have different take off, he adds, "is if materials are a temperature at which most organome- reasons for developing efficient alkane found that make a big commercial im tallic complexes decompose, says Gold dehydrogenations. Goldman's primary in pact. Then companies will say they've man. "The fact that this catalyst survives terest is in finding better ways of gener got to do things this way."^ such a high temperature opens the pos ating the alkene products. Alkenes are in has a patent on the technology, which Symyx has licensed. "Symyx is really thefirstcompany try ing to do this in a big way," DiSalvo says. LBNL and Symyx groups are hunting for phosphors that are based on metal oxides, such as those of gadolinium, alu minum, europium, and yttrium. They hope these will prove to be useful alter natives to conventional sulfur-containing phosphors, which are highly efficient but are chemically and mechanically less stable. "There's a lot of opportunity for new phosphors in oxide materials," Xiang notes. So far, the results have been "surpris ingly good," Xiang says. "In almost every library we identify at least one new mate rial. Some of those we identify are show ing to be very promising for replacing existing materials." Symyx's red phosphor compound
Promising catalyst for alkane dehydrogenation
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DECEMBER 8, 1997 C&EN 25
